EXAM 4 ADHD and Narcolepsy Dr. Pond

Question 1

Which NTs are involved alertness in therefore play a role in narcolepsy?

Answer 1

NE: locus coeruleus (LC)

Dopamine: substantia nigra, VTA, ventral periaqueductal grey

Question 2

Which drugs are used for the treatment of narcolepsy?

Answer 2

-Amphetamine (D and L-form), Dextroamphetamine (D isomer of amphetamine - more potent)
-Methylphenidate
-Modafinil (racemic mixture)
-armodafinil (active isomer of modafinil)

Question 3

What are the non-stimulant drugs for ADHD?

Answer 3

-Atomoxetine
-Viloxazine
-Clonidine
-Guanfacine

choice is based on how well the patients respond (they may switch from stimulant to non-stimulant and vice versa)

consider non-stimulants when there is a risk of abuse of stimulants

Question 4

What is the pathophysiology of ADHD?

Answer 4

not fully understood

-decreased glucose utilization in the prefrontal cortex: involved in blocking impulsivity and planning movements, logically thinking about responses

effects of stimulants on ADHD is not paradoxical (just because someone responded to stimulants doesn’t mean they have ADHD)?

Question 5

What is the definition of a psychostimulant?

Answer 5

drugs that increase dopamine in the synaptic cleft

-either through inhibition of reuptake
-through increased release

Question 6

What can be caused by drugs that increase dopamine levels?

Answer 6

-locomotor activation, tics: since it is in the nigrostriatal pathway (motor control

-can cause psychosis

-caution: with addiction

-appetite decrease: not so good for kids

all drugs that hit dopamine receptors also hit NE in some way

Question 7

MOA of Methylphenidate (Ritalin)

Answer 7

inhibits NE and Dopamine reuptake (blocks NET and DAT)
-more Dopamine and NE in the synaptic cleft

Question 8

Why does Ritalin have a short half-life?

Answer 8

it is an ester and metabolized by esterase

Question 9

MOA of Amphetamine/dextroamphetamine

Answer 9

Amph is a substrate of DAT/NET
-> uptake into the presynaptic neuron where it inhibits VMAT induced Dopamine and NE uptake into vesicles
->more DA and NE in the neuron -> released by NET/DAT back into the synaptic cleft
->in the synaptic cleft they then compete with Amph for another entry into the neuron

at higher concentrations, it also affects 5-HT
-NOTE: the release from the neuron is not from the vesicle, hence it is not regulated (release with the firing of the neuron)

Question 10

What are the serious side effects of Methylphenidate and Amphetamine/Dexamphetamine?

Answer 10

serious cardiovascular effects (sudden cardiac death)

Question 11

How is Lisdexamfetamine different from dextroamphetamine?

Answer 11

it has an L-Lysine attached to the drug = Prodrug
-> longer half-life

Question 12

MOA of Modafinil/Armodafinil

Answer 12

MOA is unknown
-probably interacts with DAT (more selectivity on parts of the brain)

-metabolized by CYP3A4

Question 13

MOA of Atomoxetine

Answer 13

NE reuptake inhibitor
-non-stimulant: since it doesn’t increase Dopamine

-ADE: suicidal ideation in children or adolescents

Question 14

MOA of Viloxazine

Answer 14

-NE reuptake inhibitor (NET inhibitor) -> helps with attention

-5-HT2B antagonist
-5-HT2C agonist
-> helps with locomotor activity (prevent tics)

-strong CYP1A2 inhibitor

Question 15

MOA of Clonidine

Answer 15

α2agonist

-α2 on the presynaptic neuron are autoreceptors and inhibitory, but on the postsynaptic site it will cause NE release

it targets the α2 receptor on the postsynaptic site

opposite adverse effects:
hypotension, sedation, fatigue
GI: nausea, abdominal pain, constipation
dry mouth
-> because in different parts of the brain it can hit presynaptically (inhibitory autoreceptors)

Question 16

MOA of Guanfacine

Answer 16

α2A agonist (postsynaptic)
-more selective (α2A) -> less hypotension

Question 17

What are the long-term side effects of stimulants?

Answer 17

hallucinations
-termor
-loss of consciousness
-irratibility
-anxiounsness
-restlessness
-delirium
-panic
-paranoia

->psychotic side effects

Question 18

Long-term side effects of Methamphetamine

Answer 18

-damage of DA and 5-HT nerve terminals
-decreased DA related activities (reduced motor speed) and impaired verbal learning
-structural and functional deficits in areas of the brain: emotions (depression and anxiety), memory

-risk for HIV: needle use, increase of viral load in the brain

Question 19

MOA of Cocaine

Answer 19

inhibits DAT, NET, and SERT

-it is also a local anesthetic (no i before caine = Ester)

Question 20

What side effect is seen with Cocaine but not with other stimulants?

Answer 20

seizure
->high doses of local anesthetics can cause seizure due to inhibiting the descending inhibitory pathway

Question 21

What are the Bath salts?

Answer 21

Synthetic cathinone

-methylenedioxypyrovalerone (MDPV)
-Mephedrone (4MMC)
-Methylone (MDMC)

structurally altered:
-alpha-Pyrrolidinopentiophenone(alpha PVP)
-ethylone

Question 22

MOA of synthetic cathinone (bath salts)

Answer 22

-NET and DAT inhibitor +/- SERT
or
-substrate of the transporter that increases the release of NE or DA

Question 23

MOA of Methylenedioxymethamphetamine
(Ecstasy/Molly, MDMA)

Answer 23

not really a stimulant but very similar

-the same MOA as amphetamine but it targets Serotonin (increases release of 5-HT + competes for reuptake)
-may also target DA and NE

-depletion of serotonin, at the next day there is lack of serotonin and it takes time to build it back up

-fosters feelings of intimacy and and empathy
-Serotonin regulates temperature -> Hyperthermia

Question 24

What are the Xanthines?

Answer 24

-Caffeine: used for headache
-Theophylline: used in COPD, asthma, apnea in prematurity
-Theobromine

-mild stimulant property, revelation in mood, decreased fatigue, increased performance

Question 25

MOA of Xanthines

Answer 25

adenosine receptor antagonist

-adenosine is a breakdown product of ATP and acts on adenosine receptors (A1, A2, A3)

-patients undergoing an adenosine stress test should avoid coffee or chocolate bc they contain caffeine and chocolate contains theophylline